Current pharmaceutical biotechnology最新文献

{"title":"A Study on the Mechanism of Action of Isorhamnetin in the Treatment of Depression using Network Pharmacology, Molecular Docking Technology,\u0000and Experimental Validation","authors":"Lei Zhang, Shiming Wang, Ying Li, Xiaoyu Li, Yue Yang, Luyao Wang, He Bai","doi":"10.2174/0113892010485402260818104814","DOIUrl":"10.2174/0113892010485402260818104814","url":null,"abstract":"<p><strong>Introduction: </strong>This study aimed to investigate the antidepressant mechanism of isorhamnetin based on the common targets and signaling pathways shared by depression and type 2 diabetes mellitus</p><p><strong>Method: </strong>The targets and mechanisms of isorhamnetin's action on depression were investigated by network pharmacology and molecular docking experiments, combined with 100 ns molecular dynamics simulation to verify the binding stability, and the effects of the related mechanisms were verified at the animal level, including Western blot analysis of p-GSK-3β phosphorylation.</p><p><strong>Result: </strong>The results showed that isorhamnetin could act on 80 potential targets and participate in the regulation of 198 related signaling pathways in the treatment of depression. It exerted potential antidepressant effects by improving glucose metabolism disorders in mice and regulating the signaling pathways comorbid with depression and diabetes.</p><p><strong>Discussion: </strong>An in-depth topological analysis demonstrated that isorhamnetin exhibited the highest degree of interaction. Direct inhibition of depression proteins by isorhamnetin and GSK-3β was validated using reverse docking validation. The effect of isorhamnetin on diabetic mice showed that isorhamnetin inhibits the activity of dipeptidyl peptidase-4 in a dose-dependent manner, promoting the secretion of glucagon-like peptide-1, and then inhibiting the activity of GSK- 3β, which contributes to the lowering of blood glucose while activating the PI3K/AKT signaling pathway, triggering a cascade reaction that subsequently regulates the expression profiles of depression- associated targets in the downstream signaling pathway. Data obtained via molecular docking experiments demonstrated that isorhamnetin binds to GSK-3β in the vicinity of its catalytic region, thereby blocking the binding of GSK-3β to its target substrate.</p><p><strong>Conclusion: </strong>This study elucidated the mechanism by which isorhamnetin exerts potential antidepressant effects by regulating the common targets and signaling pathways of depression and diabetes, and provided a theoretical basis for its clinical application.</p>","PeriodicalId":10881,"journal":{"name":"Current pharmaceutical biotechnology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148891207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Infosomes Define a New Paradigm in Inflammasome-Driven Intercellular Communication.","authors":"Semin Lee, Seungmin Lee, Hyuk-Kwon Kwon","doi":"10.2174/0113892010517341260824094057","DOIUrl":"https://doi.org/10.2174/0113892010517341260824094057","url":null,"abstract":"","PeriodicalId":10881,"journal":{"name":"Current pharmaceutical biotechnology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148891142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent Advances in the Development of Novel Strategies for LongCirculating Drug Formulation.","authors":"Phei Er Kee, Ching Siang Tan, Siew Keah Lee, Yik-Ling Chew, Tengfei Xu, A B M Helal Uddin, Xuerong Yang, Xiaoping Jin, Yifei Chen, Kai Bin Liew","doi":"10.2174/0113892010467515260729055959","DOIUrl":"https://doi.org/10.2174/0113892010467515260729055959","url":null,"abstract":"<p><strong>Introduction: </strong>Many therapeutic agents exhibit limited clinical effectiveness due to their poor bioavailability, rapid systemic clearance, and short plasma half-life, which eventually reduce patient compliance. To address these challenges, long-circulating drug delivery systems have been introduced to prolong drug presence in the bloodstream, enhance pharmacokinetic stability, and improve therapeutic outcomes.</p><p><strong>Methods: </strong>This narrative review was conducted through a structured literature search of the Scopus database using the keywords \"long-circulating AND drug formulation\" and \"long-circulating AND nanoparticles,\" focusing on articles published between 2000 and 2024.</p><p><strong>Results: </strong>This review offers a comprehensive overview of current strategies to extend drug circulation time, including PEGylation, lipidation, nucleic acid modification, and fusion technologies involving Fc and Human Serum Albumin (HSA). Additionally, the emerging cell-mediated biomimetic approaches that utilize natural biological mechanisms for targeted and sustained drug release are discussed. Furthermore, advanced formulation systems such as microencapsulation, nanocrystal suspensions, multivesicular liposomes, and biomineralization-based nanocarriers are assessed in terms of their design principles, preparation techniques, and mechanisms of controlled drug release.</p><p><strong>Discussion: </strong>These findings highlight the growing importance of rational design in longcirculating drug delivery systems, where modifications at the molecular and formulation levels can significantly influence pharmacokinetic behaviour. The shift from conventional modification strategies toward biomimetic and hybrid systems reflects an evolving focus on achieving more precise and biologically responsive drug delivery.</p><p><strong>Conclusion: </strong>Long-circulating drug delivery systems play a vital role in overcoming pharmacokinetic limitations, enhancing drug stability, and improving therapeutic efficacy. Continued advancements in formulation strategies and emerging technologies are expected to further support the development of safer, more effective, and patient-friendly precision therapeutics.</p>","PeriodicalId":10881,"journal":{"name":"Current pharmaceutical biotechnology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148886193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Uncovering Immunometabolic Mechanisms and Biomarkers in Diabetic Foot Ulcers: A Multi-omics Approach.","authors":"Guang Zeng, Yi Huang, Junsheng Hu, Mengfan Li, Ming Tian, Rong Huang, Yongzhi Jin","doi":"10.2174/0113892010486308260817144135","DOIUrl":"https://doi.org/10.2174/0113892010486308260817144135","url":null,"abstract":"<p><strong>Background: </strong>Abnormal lipid metabolism plays a crucial role in diabetic foot ulcers (DFU). This study aims to systematically uncover the cell-specific mechanisms of lipid metabolism disorders in DFUs and screen for potential diagnostic biomarkers.</p><p><strong>Methods: </strong>Bulk and single-cell transcriptomic data related to DFUs were integrated from the GEO database. Key cell types were identified through single-cell analysis, and candidate genes were screened by combining differential expression analysis with a lipid metabolism gene set. Random forest analysis, Elastic Net regression, and expression validation were subsequently performed to identify core genes, followed by the construction and validation of a nomogram model. The biological functions of the identified core genes were further investigated using immune infiltration analysis, cell subset analysis, pseudotemporal trajectory inference, and molecular docking.</p><p><strong>Results: </strong>Single-cell analysis identified macrophages as key cells in DFU, yielding 19 lipid metabolism-related candidate genes, with CCL3 and ADAP2 ultimately confirmed as core genes. The nomogram model based on these two genes exhibited good predictive performance (AUC=0.909). Macrophages were classified into three functionally heterogeneous subsets (Macro_ADAP2⁷, Macro_CCL3⁷, and Macro_IGKC⁷), and pseudotemporal analysis revealed their dynamic evolution from inflammation to metabolic regulation. Molecular docking suggested that Wortmannin and BX-471 could stably bind to ADAP2 and CCL3, respectively.</p><p><strong>Discussion: </strong>This single-cell study uncovers a central role for disordered macrophage lipid metabolism in DFU. Heterogeneous expression of CCL3 and ADAP2 defines functional macrophage subsets, linking lipid abnormalities to immune dysfunction and yielding a high-value diagnostic model with drug-target potential for precision interventions.</p><p><strong>Conclusion: </strong>This study provides new insights into elucidating the immunometabolic regulatory mechanisms of DFU and developing targeted therapies.</p>","PeriodicalId":10881,"journal":{"name":"Current pharmaceutical biotechnology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148886235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Eco-Friendly Silver Nanoparticles Synthesized from an Alkaloid-Rich Extract of Androcymbium palaestinum: Optimization, Characterization, and Activity Against Antibiotic-Resistant Bacteria.","authors":"Nusaiba Al-Nemrawi, Tamam El-Elimat, Alaa Alnaji, Majed Masadeh, Maram B Alhawarri, Sukaina Nimrawi","doi":"10.2174/0113892010469888260805100554","DOIUrl":"https://doi.org/10.2174/0113892010469888260805100554","url":null,"abstract":"<p><strong>Introduction: </strong>Silver Nanoparticles (AgNPs) can be used as antimicrobial agents. Most chemical methods used to prepare AgNPs involve toxic and hazardous materials. Fortunately, \"green nanotechnology\" is considered safe, environmentally friendly, rapid, viable, scalable, and cost-effective. This method uses microorganisms or plant extracts to fabricate AgNPs. Androcymbium palaestinum is reported to be a rich source of phenethyisoquinoline alkaloids that can be used to prepare AgNPs. The major aim of this work is to prepare AgNPs using the methanolic extract of the corms of A. palaestinum. The prepared nanoparticles were expected to be influenced by different experimental variables and to exhibit antibacterial activity against resistant bacterial strains.</p><p><strong>Methods: </strong>The methanolic extract of the corms of A. palaestinum was used for the green synthesis of Silver Nanoparticles (AgNPs-AP). The effects of pH and the concentration of the inorganic precursor, AgNO3, on the synthesis of nanoparticles were investigated. The particle size, dispersity, and surface charge of AgNPs-AP were determined. The formation of nanoparticles was confirmed using UV-Vis, XRD, FTIR, and SEM.</p><p><strong>Results: </strong>The results showed that AgNPs-AP were formed only in alkaline media. Increasing the concentration of AgNO3 decreased the sizes of the NPs, lowered their charge, and enhanced their uniformity. SEM images showed spherical and well-dispersed nanoparticles. The antibacterial activity of the AgNPs-AP was assessed by determining the Minimum Bactericidal Concentration (MBC) for resistant strains of Escherichia coli and Staphylococcus aureus. Both strains were sensitive to AgNPs-AP.</p><p><strong>Discussion: </strong>These observations highlight how green synthesis conditions strongly influence nanoparticle quality and biological performance. The behavior of AgNPs-AP suggests that A. palaestinum extract provides effective reducing and stabilizing agents, enabling environmentally friendly production of functional antimicrobial nanoparticles.</p><p><strong>Conclusion: </strong>Using A. palaestinum extract to prepare AgNPs-AP as described in this work is eco-friendly and can be used in the future to prepare an antimicrobial agent that affects resistant bacteria.</p>","PeriodicalId":10881,"journal":{"name":"Current pharmaceutical biotechnology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148863832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Carnosol Attenuates Neointimal Hyperplasia in Spontaneously Hypertensive Rats: A Network Pharmacology, Molecular Docking, and Experimental Validation Study Targeting the PPAR-γ/AGTR1 Pathway.","authors":"Jingyi Song, Meixian Chen, Daqian Gu","doi":"10.2174/0113892010481177260803111622","DOIUrl":"https://doi.org/10.2174/0113892010481177260803111622","url":null,"abstract":"<p><strong>Introduction: </strong>The study aims to investigate the effects of Carnosol on hypertensive vascular complications and its underlying mechanism.</p><p><strong>Methods: </strong>In vitro, A10 VSMCs were treated with angiotensin II (Ang II), Carnosol (various concentrations), and/or PPAR-γ inhibitor GW9662. Cell proliferation was detected by MTT assay, EdU staining, and immunoblotting for Proliferating Cell Nuclear Antigen (PCNA); cell migration was assessed by scratch wound assay and Transwell assay; oxidative stress was evaluated via dihydroethidium (DHE) staining, and measurements of malondialdehyde (MDA), Total Antioxidant Capacity (T-AOC), Superoxide Dismutase (SOD) activity, and NADPH oxidase 4 (NOX4) expression. Network pharmacology and molecular docking were used to predict target binding. In vivo, Spontaneously Hypertensive Rats (SHR) with carotid balloon injury were treated with Carnosol for 2 weeks, and related pathological and biochemical indices were detected.</p><p><strong>Results: </strong>Carnosol dose-dependently inhibited Ang II-induced VSMC proliferation and migration, reduced ROS and MDA levels, and restored T-AOC and SOD activity. It downregulated NOX4 and Ang II receptor type 1 (AGTR1) expression while enhancing PPAR-γ nuclear translocation and activity. These effects were reversed by GW9662. Molecular docking showed Carnosol directly bound to PPAR-γ (MM‑GBSA binding free energy: -33.18 kcal/mol). In SHR, carnosol significantly reduced the intima-to-media ratio, decreased MDA, restored T-AOC, suppressed PCNA, and upregulated PPAR-γ in injured arteries (all P < 0.05).</p><p><strong>Discussion: </strong>These findings align with PPAR-γ's role in vascular homeostasis, confirming Carnosol's direct binding to PPAR-γ to suppress Ang II/AGTR1-mediated oxidative stress and VSMC dysfunction.</p><p><strong>Conclusion: </strong>Carnosol mitigates hypertension-induced VSMC dysfunction and neointimal hyperplasia by regulating the PPAR-γ/AGTR1 signaling axis.</p>","PeriodicalId":10881,"journal":{"name":"Current pharmaceutical biotechnology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Formulation and Characterization of Lipidic Vesicles Utilizing CCD for Enhanced Permeation of Phenylephrine HCl for Prevention of CIA.","authors":"Ravi Shankar, Prabhat Kumar Upadhyaya, Manish Kumar, Harish Chandra Verma","doi":"10.2174/0113892010405371260605061237","DOIUrl":"https://doi.org/10.2174/0113892010405371260605061237","url":null,"abstract":"<p><strong>Introduction: </strong>Chemotherapy-induced alopecia (CIA) is a common and distressing side effect of cancer therapy. Phenylephrine hydrochloride can reduce follicular exposure to chemotherapeutic drugs through localized vasoconstriction, but its topical effectiveness is limited by poor skin penetration. Invasomal nanocarriers provide an efficient platform for enhancing dermal delivery and sustaining local drug action Methods: A rotatable three-level two-factor Central Composite Design (CCD) was employed to optimize invasomal formulations. The optimized invasomal dispersion was formulated using lipoid 80, and D-limonene was incorporated into a Carbopol-based hydrogel for sustained drug release. Formulations were characterized for vesicular morphology, zeta potential, drug entrapment, in vitro drug release, and ex vivo permeation studies using goat skin. Statistical models were validated using ANOVA.</p><p><strong>Results: </strong>The optimized formulation exhibited a vesicle size of 162 ± 1.8 (nm), EE% of 63.09 ± 3.2 %, and a steady-state flux of 0.6251 µg/cm²/h-over fivefold higher than the conventional gel. Optimization was performed using a Central Composite Design based on phospholipid and terpene concentrations. The invasomal gel exhibited significantly higher cumulative drug permeation (59.34 ± 2.34%) compared to the conventional gel (19.97 ± 0.86%) (p < 0.005), confirming enhanced dermal delivery. Drug release followed a Higuchi diffusion model, indicating controlled and sustained release for deeper dermal penetration.</p><p><strong>Discussion: </strong>The results compellingly demonstrate that the phenylephrine-loaded invasomal gel markedly outperforms conventional formulations by achieving superior dermal penetration and sustained drug release. This optimized nanocarrier system presents a transformative, non-invasive strategy for combating chemotherapy-induced alopecia.</p><p><strong>Conclusion: </strong>The developed phenylephrine-loaded invasomal gel demonstrated superior drug penetration and sustained release, suggesting its potential as a novel, non-invasive strategy for chemotherapy-induced alopecia management. Future studies should focus on in vivo validation and long-term stability assessments for clinical translation.</p>","PeriodicalId":10881,"journal":{"name":"Current pharmaceutical biotechnology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural Characterisation of Monoclonal Antibody Based on LC-MS: A General Method.","authors":"Huairu Tian, Chen Zhang, Qian Li, Siyuan Wang, Junjie Shen, Shuqiang Zhao, Le Guo, Guolin Zhang","doi":"10.2174/0113892010482038260729050308","DOIUrl":"https://doi.org/10.2174/0113892010482038260729050308","url":null,"abstract":"<p><strong>Introduction: </strong>To establish a universal method based on LC-MS for the structural characterization of mAbs. This method includes determining the intact molecular weight, deglycosylated intact molecular weight, reduced molecular weight, and deglycosylated-reduced molecular weight of mAbs, along with peptide mapping (amino acid sequence coverage) and glycan profiling.</p><p><strong>Methods: </strong>LC-MS analysis was performed using mAb injections as test samples. A MAbPac™ RP column was coupled to intact mass spectrometry for molecular weight measurement. For peptide mapping, trypsin-digested samples were analyzed using an ACQUITY UPLC Peptide CSH C18 column with tandem mass spectrometry (MS/MS) to assess amino acid sequence coverage. Glycan profiling was performed using an ACQUITY UPLC Glycan BEH Amide column, with 2-ABlabeled glycans analyzed via secondary mass spectrometry.</p><p><strong>Results: </strong>For bevacizumab (three manufacturers), sintilimab, and camrelizumab, the intact molecular weight, deglycosylated molecular weight, reduced molecular weight, and deglycosylatedreduced molecular weight of mAbs showed errors of less than 10 ppm when compared with theoretical sequences, confirming consistency with theoretical values. Peptide mapping demonstrated that the amino acid sequence coverage of bevacizumab and sintilimab matched the theoretical sequences. Glycan profiling identified distinct glycan profiles for the tested mAbs.</p><p><strong>Discussion: </strong>A universal LC-MS-based method was developed for comprehensive structural characterization of monoclonal antibodies, including molecular weight, peptide mapping (sequence coverage), and glycan profiling. The method is efficient, straightforward, and validated across three mAb therapeutics, providing reliable support for the development and analysis of mAbbased therapeutics.</p><p><strong>Conclusion: </strong>This method allows companies to directly apply it to quality control. It has been validated with several target biologics, demonstrating its versatility and general applicability.</p>","PeriodicalId":10881,"journal":{"name":"Current pharmaceutical biotechnology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative Phytotherapy for Neurodegenerative Disorders: Bridging Traditional Botanicals, Bioactive Compounds, and Nanotechnology.","authors":"Shatrudhan Prajapati, Shikha Yadav, Ajay Pal Singh, Kuldeep Singh, Divya Jain, Jeetendra Kumar Gupta, Mukesh Chandra Sharma","doi":"10.2174/0113892010419603260127123920","DOIUrl":"https://doi.org/10.2174/0113892010419603260127123920","url":null,"abstract":"<p><p>Neurodegenerative disorders (NDDs) such as Alzheimer's, Parkinsons etc., are progressive and debilitating conditions that have little therapeutic intervention. Existing pharmacological interventions mainly provide symptomatic relief and do not respond to the pathophysiology of these diseases, which is complex and multifactorial and includes oxidative stress, mitochondrial dysfunction, neuroinflammation, and protein misfolding. The synthesis of emerging evidence regarding the neuroprotective efficacy of phytotherapy is presented in this review, and the focus is on such traditional medicinal plants as Bacopa monnieri, Withania somnifera, and Centella asiatica. These botanicals have multi-target actions via bioactive compounds, such as bacosides, withanolides, and curcuminoids, that modulate cholinergic function and counteract the aggregation of amyloid beta residues, as well as support the integrity of mitochondria. The advanced delivery systems, like nano-formulations, are also highlighted in the review to improve the bioavailability and therapeutic efficacy. Along with pharmacological processes, integrative approaches that involve the use of phytotherapy, along with lifestyle changes and conventional medicine, are considered. Finally, this holistic model will help to shift phytotherapy to a primary approach to slowing neurodegeneration and enhancing the quality of life. The future directions are the clinical validation, standardization of compounds, and integration into personalized medicine models.</p>","PeriodicalId":10881,"journal":{"name":"Current pharmaceutical biotechnology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148789245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging Pharmacological Therapies for Huntington's Disease: Translational Insights from Recent Clinical Trials.","authors":"Bhupesh Chander Semwal, Kuldeep Singh, Ritesh Sharma, Deepak Sharma, Abhishek Sharma, Divya Jain, Mukesh Chandra Sharma","doi":"10.2174/0113892010447442260727092257","DOIUrl":"https://doi.org/10.2174/0113892010447442260727092257","url":null,"abstract":"<p><p>Huntington's disease [HD] is a progressive, autosomal dominant neurodegenerative disorder caused by a pathogenic CAG repeat expansion in the HTT gene, resulting in mutant huntingtin [mHTT] protein accumulation, neuronal dysfunction, and selective neurodegeneration. Current pharmacological management remains largely symptomatic, with no approved therapies capable of modifying disease progression. In recent years, however, significant advances in molecular neuroscience and translational medicine have accelerated the development of disease-modifying strategies targeting the underlying pathogenic mechanisms of HD. This review synthesizes emerging pharmacological therapies with a particular focus on insights derived from recent and ongoing clinical trials. Key therapeutic approaches discussed include gene-silencing technologies such as antisense oligonucleotides, RNA interference, and CRISPRCas9- based strategies, as well as small-molecule modulators targeting mutant huntingtin aggregation, proteostasis, autophagy, mitochondrial dysfunction, and neuroinflammation. In addition, advances in symptomatic treatments addressing motor, cognitive, and psychiatric manifestations are reviewed. The article critically examines translational challenges encountered in clinical development, including blood-brain barrier penetration, allele selectivity, dosing paradigms, patient heterogeneity, biomarker integration, and ethical considerations associated with irreversible genetic interventions. Lessons learned from both successful and failed trials highlight the importance of precision medicine approaches, biomarker-guided trial designs, and combination therapies targeting multiple pathogenic pathways. Collectively, this review provides an updated and clinically relevant overview of the evolving HD therapeutic landscape and outlines key considerations for translating molecular advances into effective and safe pharmacological interventions.</p>","PeriodicalId":10881,"journal":{"name":"Current pharmaceutical biotechnology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148705739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}